Examination of a wide variety of Simian Virus 40 mutant and defective genomes shows that, with one possible exception, they all have retained, in addition to the replication origin at map position 0.67, either a portion of the viral DNA near map position 0.16 or a host DNA substitution. The requirement for the viral termination region is particularly strict in A172 cells, a human glioblastoma line which supports the lytic growth of SV40 and rapidly accumulates a high proportion of defectives, even on low multiplicity passage of the virus. This has led to the hypothesis that the termination region, or sequences substituting for it in function, is required in cis for propagation. By use of appropriate restriction enzymes, variant viral genomes lacking the termination region will be constructed and tested for viability on co-transfection with non-defective DNA. The ability of the viral termination region and of host cell sequences recovered from natural defectives to restore viability to non-propagatable variants will be examined. If the necessity of retaining the termination region is confirmed, its role in the lytic cycle will be investigated in studies of the replication and transcripton of various defectives. The differences between A172 cells and monkey cells with respect to their treatment of defectives will be examined. First, natural defectives accumulated in one cell type will be tested for their viability and competitive advantage in the other host. Second, matabolic parameters of the cells before and after infection will be measured which may be relevant to the generation and accumulation of defectives. Such cell characteristics may be generally important in determining which tissues are subject to acute and which to persistent infection by many viruses.